RESUMO
PURPOSE: This study aims to evaluate whether the use of citicoline oral solution could improve quality of life in patients with chronic open-angle glaucoma (OAG). DESIGN: Randomized, double-masked, placebo-controlled, cross-over study was used. Patients were randomized to one of the two sequences: either citicoline 500 mg/day oral solution-placebo or placebo-citicoline 500 mg/day oral solution. Switch of treatments was done after 3 months; patients were then followed for other 6 months. Follow-up included 3-month, 6-month, and 9-month visits. OUTCOMES: The primary outcome was the mean change of "intra-patient" composite score of the Visual Function Questionnaire-25 (VFQ-25). after citicoline oral solution vs placebo at 6-month visit as compared with baseline. METHODS: The trial was multicenter, conducted at 5 European Eye Clinics. OAG patients with bilateral visual field damage, a mean deviation (MD) ranging from - 5 to - 13 dB in the better eye, and controlled IOP were included. VFQ-25 and SF-36 questionnaires were administered at baseline and at 3-, 6-, and 9-month visits. A mixed effect model, with a random effect on the intercept, accounted for correlations among serial measurements on each subject. RESULTS: The primary pre-specified outcome of the analysis reached statistical significance (p = 0.0413), showing greater improvement after citicoline oral solution. There was an increase in the composite score in both arms compared to baseline, but it was significant only for the placebo-citicoline arm (p = 0.0096, p = 0.0007, and p = 0.0006 for the three time-points compared to baseline). The effect of citicoline was stronger in patients with vision-related quality of life more affected by glaucoma at baseline. CONCLUSIONS: This is the first placebo-controlled clinical study evaluating the effect of a medical treatment aiming at improving vision-related quality of life in glaucomatous patients.
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Glaucoma de Ângulo Aberto , Glaucoma , Humanos , Citidina Difosfato Colina/uso terapêutico , Glaucoma de Ângulo Aberto/tratamento farmacológico , Estudos Cross-Over , Qualidade de Vida , Pressão Intraocular , Glaucoma/tratamento farmacológicoRESUMO
Glaucoma is still a poorly understood disease with a clear need for new biomarkers to help in diagnosis and potentially offer new therapeutic targets. We aimed to determine if the metabolic profile of aqueous humor (AH) as determined by nuclear magnetic resonance (NMR) spectroscopy allows the distinction between primary open-angle glaucoma patients and control subjects, and to distinguish between high-tension (POAG) and normal-tension glaucoma (NTG). We analysed the AH of patients with POAG, NTG and control subjects (n = 30/group). 1H NMR spectra were acquired using a 400 MHz spectrometer. Principle component analysis (PCA), machine learning algorithms and descriptive statistics were applied to analyse the metabolic variance between groups, identify the spectral regions, and hereby potential metabolites that can act as biomarkers for glaucoma. According to PCA, fourteen regions of the NMR spectra were significant in explaining the metabolic variance between the glaucoma and control groups, with no differences found between POAG and NTG groups. These regions were further used in building a classifier for separating glaucoma from control patients, which achieved an AUC of 0.93. Peak integration was performed on these regions and a statistical analysis, after false discovery rate correction and adjustment for the different perioperative topical drug regimen, revealed that five of them were significantly different between groups. The glaucoma group showed a higher content in regions typical for betaine and taurine, possibly linked to neuroprotective mechanisms, and also a higher content in regions that are typical for glutamate, which can indicate damaged neurons and oxidative stress. These results show how aqueous humor metabolomics based on NMR spectroscopy can distinguish glaucoma patients from controls with a high accuracy. Further studies are needed to validate these results in order to incorporate them in clinical practice.
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Humor Aquoso/metabolismo , Cirurgia Filtrante/métodos , Glaucoma/metabolismo , Pressão Intraocular/fisiologia , Metabolômica/métodos , Idoso , Biomarcadores/metabolismo , Estudos Transversais , Feminino , Glaucoma/fisiopatologia , Glaucoma/cirurgia , Humanos , MasculinoRESUMO
PURPOSE: To compare funduscopic and confocal scanning vertical cup-disc ratio (VCDR) assessments and their respective predictive value for estimating functional glaucomatous damage. METHODS: Data from a single eye of open angle glaucoma patients from the Leuven Eye Study were included: age, gender, intra-ocular pressure, visual acuity, refractive error, visual field mean deviation and pattern standard deviation, funduscopic and HRT III VCDRs as well as mean retinal nerve fibre layer thickness. Non-parametric tests to compare differences within and between diagnostic groups were used, and receiver-operating characteristic curves as well as Bland-Altman plots constructed. RESULTS: Three hundred and one eyes of 301 subjects with primary open angle glaucoma (POAG) and normal tension glaucoma (NTG) were included. The average VCDR assessed with HRT III was significantly smaller than the funduscopic measurement (0.69 ± 0.16 vs. 0.81 ± 0.14, respectively; p < 0.001). The predictive value of both measurement techniques did not differ in NTG patients, but the funduscopic estimate yielded a significantly larger predictive power in patients with severe POAG. CONCLUSION: Funduscopic and confocal scanner estimates of VCDR differ significantly and should not be used interchangeably. In POAG patients with severe glaucoma, a subjective VCDR predicts functional glaucomatous damage significantly better.
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Glaucoma de Ângulo Aberto/diagnóstico , Pressão Intraocular/fisiologia , Glaucoma de Baixa Tensão/diagnóstico , Microscopia Confocal/métodos , Oftalmoscopia/métodos , Disco Óptico/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Idoso , Estudos Transversais , Feminino , Fundo de Olho , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Glaucoma de Baixa Tensão/fisiopatologia , Masculino , Campos VisuaisRESUMO
PURPOSE: To determine the efficacy and safety of ocriplasmin for vitreomacular traction (VMT) resolution and to study changes in optic disk and peripapillary region. METHODS: Retrospective, single-center, observational case series. In 38 eyes with VMT (10 with concomitant full-thickness macular hole), determined by optical coherence tomography, a single intravitreal injection of ocriplasmin was administered. Baseline ocular characteristics included the presence/absence of epiretinal membrane, lens status, and vitreomacular adhesion size. Spectral domain optical coherence tomography and Heidelberg retinal tomography were performed at baseline and follow-up visits. RESULTS: A total of 71.1% of eyes treated with ocriplasmin had VMT resolution, improving to 83.9% after applying MIVI-TRUST selection criteria. A total of 90% of eyes with full-thickness macular hole showed VMT resolution, with 40% of those achieving full-thickness macular hole closure. Subretinal fluid in the macular region was observed in 36.8% of eyes 1 day after injection, and all cleared spontaneously by Day 42. A significant difference was observed in cup/disk area ratio between patients who achieved VMT resolution and patients who did not. CONCLUSION: Careful patient selection improves ocriplasmin efficacy. Transient optic disk morphology changes such as decreased cup/disk area ratio may occur in patients without VMT resolution.
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Oftalmopatias/tratamento farmacológico , Fibrinolisina/uso terapêutico , Fibrinolíticos/uso terapêutico , Disco Óptico/patologia , Fragmentos de Peptídeos/uso terapêutico , Doenças Retinianas/tratamento farmacológico , Corpo Vítreo/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Oftalmopatias/diagnóstico , Feminino , Fibrinolisina/efeitos adversos , Fibrinolíticos/efeitos adversos , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Fragmentos de Peptídeos/efeitos adversos , Doenças Retinianas/diagnóstico , Estudos Retrospectivos , Aderências Teciduais/tratamento farmacológico , Resultado do Tratamento , Corpo Vítreo/patologiaRESUMO
Intraocular pressure (IOP) measurement is the cornerstone of the management of glaucoma patients. The gold standard for assessing IOP is Goldmann applanation tonometry (GAT). Recently, the dynamic contour tonometer (DCT) has become available. While both devices provide reliable IOP measurements, the results are not interchangeable. DCT has the advantage of measuring an additional parameter: ocular pulse amplitude (OPA). OPA is defined as the difference between systolic and diastolic IOP and represents the pulsatile wave front produced by the varying amount of blood in the eye during the cardiac cycle. It has been shown to vary with ocular structural parameters, such as axial length, corneal thickness, and ocular rigidity, as well as with systemic variables like heart rate, blood pressure, and left ventricular ejection fraction. Although the existence of some of these associations is still controversial, the clinical relevance of OPA has been consistently suggested, especially in glaucoma. Further research on this intriguing parameter could not only provide insight into glaucoma pathophysiology but also help integrate this variable into clinical practice.
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Pressão Sanguínea/fisiologia , Frequência Cardíaca/fisiologia , Pressão Intraocular/fisiologia , Tonometria Ocular , Glaucoma/fisiopatologia , HumanosRESUMO
PURPOSE: To investigate the relationship between optic nerve sheath diameter (ONSD) and retrobulbar blood flow velocities, as measured by color Doppler imaging (CDI) in glaucoma patients. METHODS: We performed a prospective, randomized, observer-masked study involving a total of 197 subjects. Once enrolled, they were divided by three groups: healthy controls (n = 51), normal-tension glaucoma patients (NTG, n = 58), and primary, open-angle glaucoma patients (POAG, n = 88). All subjects underwent a general ophthalmological examination, an ultrasound-based assessment of the ONSD, and a hemodynamic study of the retrobulbar vascularization using CDI. Non-parametric tests, chi-square contingency tables, and the Deming correlations were used to explore differences and correlations between variables in the diagnostic groups. RESULTS: ONSD was not different between experimental groups (p = 0.28). ONSD correlated positively with the pulsatility index of the ophthalmic artery in healthy individuals (p = 0.007), but not in glaucoma patients (NTG: p = 0.41; POAG: p = 0.22). In NTG patients, higher ONSD values were associated with lower end-diastolic and mean flow velocities in the short ciliary arteries (p = 0.005 in both correlations). No such correlation was found in healthy nor POAG groups (p range between 0.15 to 0.96). ONSD was not associated with any CDI-related variable of the central retinal artery in any cohort. Venous outflow velocities were not associated with ONSD in any of the three groups. CONCLUSIONS: ONSD is negatively correlated with retrobulbar blood flow velocities in glaucoma patients, but not in healthy controls.
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Artérias Ciliares/fisiologia , Glaucoma de Ângulo Aberto/fisiopatologia , Glaucoma de Baixa Tensão/fisiopatologia , Bainha de Mielina/patologia , Artéria Oftálmica/fisiologia , Nervo Óptico/patologia , Artéria Retiniana/fisiologia , Idoso , Anti-Hipertensivos/uso terapêutico , Velocidade do Fluxo Sanguíneo , Método Duplo-Cego , Feminino , Glaucoma de Ângulo Aberto/tratamento farmacológico , Humanos , Pressão Intraocular/fisiologia , Glaucoma de Baixa Tensão/tratamento farmacológico , Masculino , Estudos Prospectivos , Tonometria Ocular , Ultrassonografia Doppler em Cores , Acuidade Visual/fisiologiaRESUMO
PURPOSE: To assess a change in visual-related quality of life (QoL) in glaucoma patients after switching from preservative-containing medical therapy to preservative-free unit dose timolol/dorzolamide fixed combination (TDFC UD). METHODS: Prospective, noninterventional, multicenter 8-week study. Primary outcome was a change in visual symptoms at week 8, as assessed by the Glaucoma Symptom Scale (GSS). RESULTS: 80 patients completed the study. There was a clinically significant increase in the scores of all GSS-related categories at week 8 when compared to baseline (GSS symptom week 8: +21.15 ± 37.9%, GSS function week 8: +10.3 ± 31.6%, both p < 0.001 vs. baseline). Comparison between patients taking only TDFC UD and patients taking TDFC UD plus concomitant medications did not detect differences in any GSS category (p > 0.50 in all comparisons). CONCLUSIONS: Switching to TDFC UD significantly improved the self-reported QoL of glaucoma patients. This can be seen even in patients who are taking concomitant ocular treatments.
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Anti-Hipertensivos/uso terapêutico , Glaucoma de Ângulo Aberto/tratamento farmacológico , Glaucoma de Ângulo Aberto/psicologia , Conservantes Farmacêuticos/uso terapêutico , Qualidade de Vida/psicologia , Sulfonamidas/uso terapêutico , Tiofenos/uso terapêutico , Timolol/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Combinação de Medicamentos , Substituição de Medicamentos , Feminino , Humanos , Pressão Intraocular/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Perfil de Impacto da Doença , Inquéritos e Questionários , Acuidade VisualRESUMO
PURPOSE: To characterize the choroidal thickness of the papillomacular region in young healthy individuals using spectral-domain optical coherence tomography (SD-OCT). METHODS: Papillary and macular SD-OCT scans were obtained using an enhanced depth imaging mode. Digital retinography was used to assess any overlapping areas and to determine the papillomacular region. Spearman's correlations were used to explore the relationship between the different regional choroidal thicknesses. RESULTS: Sixty-three volunteers aged 21.6 ± 1.1 years were included. There was a significant asymmetry in choroidal thickness throughout the 10-mm length model (p < 0.001). While the choroid was shown to thicken as the distance from the optic disc increased (p < 0.001), each of the 500-µm blocks of the papillomacular region were significantly thinner than their nasal counterparts (p < 0.02 in all pairwise comparisons). CONCLUSION: In young healthy individuals, the choroid under the papillomacular region appears to be thinner than in other areas. These differences could relate to specificities of the retina overlying this region.
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Corioide/anatomia & histologia , Macula Lutea/anatomia & histologia , Disco Óptico/anatomia & histologia , Feminino , Voluntários Saudáveis , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Tamanho do Órgão , Tomografia de Coerência Óptica , Adulto JovemRESUMO
PRCIS: In reducing intraocular pressure (IOP), Paul (PGI) and Baerveldt (BGI) glaucoma implants are safe and effective in patients with glaucoma. OBJECTIVE: To compare efficacy and safety profiles of the PGI and BGI in the treatment of medically uncontrolled glaucoma at 1 year of follow-up. METHODS: Retrospective analysis of patients implanted with a PGI or BGI with a minimum of 12 months follow-up. The primary outcome was surgical success defined as IOP ≥6 and ≤18 mm Hg and at least 20% IOP reduction from baseline. Secondary outcomes included IOP measurements, number of medications, and complications. RESULTS: Twenty-three patients implanted with PGI and 27 with BGI were included. At last visit (12 mo), mean IOP had decreased from 23.7 ± 6.9 to 0.1 ± 2.9 mm Hg in the PGI group versus 26 ± 7.3 to 10.4 ± 4.9 mm Hg with the BGI ( P < 0.001 for both comparisons). Overall qualified success rates were similar between groups (PGI 91% vs BGI 89%, P = 0.784). IOP was significantly lower in the PGI at week 1 and month 1 of follow-up versus the BGI (13.6 ± 6.1 vs 20.1 ± 7.4; 14.6±3.8 vs 21.2 ± 5.8 mm Hg; P < 0.002 for both) with a lower number of medications (1.57 ± 1.47 vs 2.52 ± 1.16 at mo 1, P = 0.015). Most complications were minor and similar in both groups. CONCLUSION: Both PGI and BGI are safe and effective in reducing IOP in patients with glaucoma, with similar success rates.
Assuntos
Implantes para Drenagem de Glaucoma , Glaucoma , Pressão Intraocular , Tonometria Ocular , Acuidade Visual , Humanos , Pressão Intraocular/fisiologia , Estudos Retrospectivos , Feminino , Masculino , Seguimentos , Idoso , Resultado do Tratamento , Pessoa de Meia-Idade , Acuidade Visual/fisiologia , Glaucoma/cirurgia , Glaucoma/fisiopatologia , Implantação de Prótese , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/administração & dosagemRESUMO
Excessive post-operative wound healing with subsequent scarring frequently leads to surgical failure of glaucoma filtration surgery (trabeculectomy). We investigated the hypothesis that placental growth factor (PlGF) plays a role in post-operative scar formation, and that it therefore may be a target for improvement of filtration surgery outcome. ELISA experiments showed that PlGF levels were significantly increased in aqueous humour of glaucoma patients and after VEGF treatment, which may indicate an important contribution of this growth factor to wound healing after trabeculectomy. Using a mouse model of glaucoma filtration surgery, we were able to show that intracameral injection of a previously characterized anti-PlGF antibody (ThromboGenics NV) significantly improved surgical outcome by increasing bleb survival and bleb area. This was associated with a significant reduction in post-operative proliferation, inflammation and angiogenesis during the first post-operative days after surgery, and with a decrease in collagen deposition at later stages. Furthermore, inhibition of PlGF seemed to be more effective than anti-VEGF-R2 treatment in improving surgical outcome, possibly via its additional effect on inflammation. These results render PlGF an appealing target for ocular wound healing and point to potential therapeutic benefits of PlGF inhibition for the prevention of surgical failure.
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Glaucoma/metabolismo , Glaucoma/cirurgia , Proteínas da Gravidez/antagonistas & inibidores , Animais , Anticorpos/administração & dosagem , Anticorpos/farmacologia , Humor Aquoso/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cicatriz/patologia , Modelos Animais de Doenças , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/patologia , Glaucoma/patologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Fator de Crescimento Placentário , Proteínas da Gravidez/metabolismo , Coelhos , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Cápsula de Tenon/patologia , Trabeculectomia , Resultado do Tratamento , Regulação para Cima/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
BACKGROUND: The mechanisms underlying conjunctival symptom reduction by nasal corticosteroids in allergic rhinoconjunctivitis are unknown. A naso-ocular reflex may be present. OBJECTIVE: To study the effects of nasal fluticasone furoate (FF) on conjunctival symptoms and substance P and histamine levels in tear fluid after nasal grass pollen provocation (GPP). METHODS: A double-blind placebo-controlled study was performed in 26 grass pollen-allergic patients. A selective GPP was performed during the grass pollen season after 2 weeks of FF or placebo treatment. Nasal and conjunctival symptoms were scored using a visual analog scale (VAS), and tear fluid was collected for measuring substance P and histamine using an enzyme-linked immunosorbent assay. RESULTS: Compared with placebo, FF reduced conjunctival symptom scores during the pollen season (-1.75 [-2.75, 0.20] vs 0.0 [0.0, 0.0]; P = .01) and after GPP at 15 minutes (0.05 [-0.42, 1.52] vs 2.05 [0.62, 3.62]; P < .001) and 1 hour (-0.45 [-1.75, 0.1] vs 0.05 [-0.97, 1.85]; P < .01). Treatment with FF decreased substance P levels in tear fluid (44.11 [32.81, 61.02] vs 65.26 [48.62, 79.73] pg/mg protein; P = .0098). Histamine levels in tear fluid showed a GPP-induced increase in the placebo group (7.26 [3.12, 9.69] vs 5.71 [2.05, 7.00] ng/mg protein; P = .02), but not in the FF group (6.77 [3.43, 13.00] vs 5.24 [3.18, 7.06] ng/mg protein; P = .08). CONCLUSION: FF nasal spray reduced conjunctival symptoms in grass pollen-allergic patients in parallel with lower substance P levels in tear fluid. These data help in understanding the reduction of conjunctival symptoms by intranasal anti-inflammatory therapy.
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Corticosteroides/administração & dosagem , Androstadienos/administração & dosagem , Conjuntivite Alérgica/tratamento farmacológico , Rinite Alérgica Sazonal/tratamento farmacológico , Substância P/metabolismo , Lágrimas/metabolismo , Administração Intranasal , Corticosteroides/efeitos adversos , Adulto , Androstadienos/efeitos adversos , Antígenos de Plantas/efeitos adversos , Antígenos de Plantas/imunologia , Túnica Conjuntiva/efeitos dos fármacos , Túnica Conjuntiva/imunologia , Conjuntivite Alérgica/complicações , Feminino , Histamina/metabolismo , Humanos , Masculino , Testes de Provocação Nasal , Seios Paranasais/efeitos dos fármacos , Seios Paranasais/imunologia , Poaceae , Pólen/efeitos adversos , Pólen/imunologia , Rinite Alérgica Sazonal/complicações , Estações do Ano , Adulto JovemRESUMO
PURPOSE: 1. Identify differences in optic nerve sheath diameter (ONSD) as an indirect measure of intracranial pressure (ICP) in glaucoma patients and a healthy population. 2. Identify variables that may correlate with ONSD in primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG) patients. METHODS: Patients with NTG (n = 46) and POAG (n = 61), and healthy controls (n = 42) underwent B-scan ultrasound measurement of ONSD by an observer masked to the patient diagnosis. Intraocular pressure (IOP) was measured in all groups, with additional central corneal thickness (CCT) and visual field defect measurements in glaucomatous patients. Only one eye per patient was selected. Kruskal-Wallis or Mann-Whitney were used to compare the different variables between the diagnostic groups. Spearman correlations were used to explore relationships among these variables. RESULTS: ONSD was not significantly different between healthy, NTG and POAG patients (6.09 ± 0.78, 6.03 ± 0.69, and 5.71 ± 0.83 respectively; p = 0.08). Visual field damage and CCT were not correlated with ONSD in either of the glaucoma groups (POAG, p = 0.31 and 0.44; NTG, p = 0.48 and 0.90 respectively). However, ONSD did correlate with IOP in NTG patients (r = 0.53, p < 0.001), while it did not in POAG patients and healthy controls (p = 0.86, p = 0.46 respectively). Patient's age did not relate to ONSD in any of the groups (p > 0.25 in all groups). CONCLUSIONS: Indirect measurements of ICP by ultrasound assessment of the ONSD may provide further insights into the retrolaminar pressure component in glaucoma. The correlation of ONSD with IOP solely in NTG patients suggests that the translaminar pressure gradient may be of particular importance in this type of glaucoma.
Assuntos
Pressão Intracraniana/fisiologia , Pressão Intraocular/fisiologia , Glaucoma de Baixa Tensão/diagnóstico , Doenças do Nervo Óptico/diagnóstico , Nervo Óptico/patologia , Idoso , Anti-Hipertensivos/uso terapêutico , Glaucoma de Ângulo Aberto/diagnóstico , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Glaucoma de Baixa Tensão/fisiopatologia , Nervo Óptico/diagnóstico por imagem , Doenças do Nervo Óptico/fisiopatologia , Tonometria Ocular , Ultrassonografia , Acuidade Visual/fisiologia , Campos VisuaisRESUMO
Topical glucocorticoids are a well-known risk factor of intraocular pressure (IOP) elevation in one third of the general population and in up to 90% of glaucomatous patients. Whether this steroid response is caused by intranasal, inhaled or systemic glucocorticoids, is less known. This study presents an overview of the current literature on the topic, thereby providing guidance on when ophthalmological follow-up is indicated. A literature study was performed in Medline, and 31 studies were included for analysis. Twelve out of fourteen studies discussing intranasal glucocorticoids show no significant association with an elevated IOP. Regarding inhaled glucocorticoids, only three out of twelve studies show a significant association. The observed increase was either small or was only observed in patients treated with high inhaled doses or in patients with a family history of glaucoma. An elevated IOP caused by systemic glucocorticoids is reported by four out of the five included studies, with one study reporting a clear dose-response relationship. This review concludes that a steroid response can be triggered in patients treated with systemic glucocorticoids. Inhaled glucocorticoids may cause a significant IOP elevation when administered in high doses or in patients with a family history of glaucoma. At present, there is no evidence for a clinically significant steroid response caused by intranasally administered glucocorticoids.
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Glaucoma remains a frequent serious complication following cataract surgery in children. The optimal approach to management for 'glaucoma following cataract surgery' (GFCS), one of the paediatric glaucoma subtypes, is an ongoing debate. This review evaluates the various management options available and aims to propose a clinical management strategy for GFCS cases. A literature search was conducted in four large databases (Cochrane, PubMed, Embase, and Web of Science), from 1995 up to December 2021. Thirty-nine studies-presenting (1) eyes with GFCS; a disease entity as defined by the Childhood Glaucoma Research Network Classification, (2) data on treatment outcomes, and (3) follow-up data of at least 6 months-were included. Included papers report on GFCS treated with angle surgery, trabeculectomy, glaucoma drainage device implantation (GDD), and cyclodestructive procedures. Medical therapy is the first-line treatment in GFCS, possibly to bridge time to surgery. Multiple surgical procedures are often required to adequately control GFCS. Angle surgery (360 degree) may be considered before proceeding to GDD implantation, since this technique offers good results and is less invasive. Literature suggests that GDD implantation gives the best chance for long-term IOP control in childhood GFCS and some studies put this technique forward as a good choice for primary surgery. Cyclodestruction seems to be effective in some cases with uncontrolled IOP. Trabeculectomy should be avoided, especially in children under the age of one year and children that are left aphakic. The authors provide a flowchart to guide the management of individual GFCS cases.
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Vascular endothelial growth factor (VEGF) plays an important role in both physiological and pathological angiogenesis. Our previous studies showed a differential role of VEGF isoforms in retinal physiological angiogenesis. We also demonstrated that non-selective inhibition of VEGF by bevacizumab had a beneficial effect on surgical outcome after glaucoma filtration surgery by reducing angiogenesis as well as fibrosis. However, the function of the VEGF isoforms in pathological angiogenesis and wound healing in the eye still remains unidentified. This study was designed to elucidate the differential roles of VEGF isoforms in scar formation after trabeculectomy. Furthermore, we also investigated whether pegaptanib (Macugen™, Pfizer), an aptamer which specifically blocks VEGF(165), could improve surgical outcome by reducing postoperative scarring. VEGF-R2 and neuropilin-1 (NRP-1) expression was analyzed in vitro by RT-PCR, and were found to be expressed at higher levels in human umbilical vein endothelial cells (HUVEC) as compared to Tenon fibroblasts (TF). The effect of the different VEGF isoforms (VEGF(121), VEGF(165) and VEGF(189)) and pegaptanib on cell proliferation was determined via WST-1 assay. Endothelial cell proliferation was stimulated after addition of VEGF(121) and VEGF(165), whereas VEGF(121) and VEGF(189) increased fibroblast growth. These effects on proliferation were associated with an activation of the ERK pathway, as revealed using the TransAM c-Myc assay. Inhibition of the ERK pathway, by PD98059 administration, significantly reduced VEGF isoform induced cell growth. A dose-dependent reduction of endothelial cell proliferation was observed after pegaptanib administration, while only the highest dose was able to inhibit fibroblast growth. Next, the in vivo effect of pegaptanib was investigated in a rabbit model of trabeculectomy. The surgical outcome was evaluated by performing clinical investigations (IOP, bleb area, height and survival), as well as histomorphometric analyses of angiogenesis (CD31), inflammation (CD45) and fibrosis (Sirius Red). A single postoperative application of pegaptanib had a beneficial impact on surgical outcome, mainly by reducing angiogenesis, but not inflammation or collagen deposition. Repeated injections slightly improved surgical outcome, but again solely by reducing angiogenesis. In summary, our results revealed that the VEGF isoforms play a differential role in ocular wound healing: VEGF(165) and VEGF(121) predominantly affect blood vessel growth, whereas VEGF(189) is rather involved in fibrosis, an important process in wound healing.
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Glaucoma/cirurgia , Malha Trabecular/patologia , Trabeculectomia , Fator A de Crescimento do Endotélio Vascular/fisiologia , Animais , Aptâmeros de Nucleotídeos/farmacologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Feminino , Fibroblastos/citologia , Fibroblastos/metabolismo , Fibrose , Humanos , Pressão Intraocular/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/fisiologia , Neuropilina-1/genética , Isoformas de Proteínas/fisiologia , RNA Mensageiro/metabolismo , Coelhos , Reação em Cadeia da Polimerase em Tempo Real , Cápsula de Tenon/citologia , Malha Trabecular/metabolismo , Veias Umbilicais/citologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Cicatrização/fisiologiaRESUMO
BACKGROUND: The purpose of this prospective study was to evaluate the efficacy and safety of the Ultrasound Cyclo Plasty (UCP) procedure using high-intensity focused ultrasound in surgery-naïve open-angle glaucoma patients. METHODS: prospective, non-randomized, single-arm, multicenter clinical trial. Sixty-six eyes with primary open-angle glaucoma, intraocular pressure (IOP) ≥21 mmHg and with no history of filtering surgery were enrolled. Patients were treated by UCP with a therapy probe comprising six piezoelectric transducers, consecutively activated for 8 s each. Complete ophthalmic examination was performed before the procedure, 1 day after the procedure, and 1, 3, 6, 12, 18 and 24 months after the procedure. Primary outcomes were complete success (defined as IOP lowering from baseline ≥20% without additional glaucoma medications) and vision-threatening complications. Secondary outcomes were the presence of complications and the reduction of the number of medications used. RESULTS: IOP was significantly reduced after one procedure (p < 0.05), from a mean pre-operative value of 24.3 ± 2.9 mmHg (n = 2.3 hypotensive medications) to a mean value of 15.9 ± 3.6 mmHg (n = 2.2 hypotensive medications) at 2 years (mean IOP lowering of 33%). Surgical success was achieved in 74% of eyes. Notwithstanding side effects such as transient anterior chamber inflammation, refractive error changes, transient hypotony and macular edema, no major intra or post-operative complications such as phthisis, induced cataract, neovascularization or significant vision loss were observed. CONCLUSIONS: Ultrasound Cyclo Plasty is a valuable, effective and well-tolerated procedure to lower IOP in patients with open-angle glaucoma without previous filtering surgery.
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IMPORTANCE: This study compares the efficacy and tolerability of a preservative-free prostaglandin analogue (tafluprost 15 mg/ml) to a prostaglandin analogue that uses 0.02% of benzalkonium chloride (bimatoprost 0.1 mg/ml). BACKGROUND: Different prostaglandin analogues have been commercially approved, with differences in tolerability. DESIGN: Prospective, randomised, investigator-masked, 3-month crossover, multicentre trial. PARTICIPANTS: Sixty-four patients with ocular hypertension or open-angle glaucoma were randomised to two groups, after a 4-week washout period from their current topical drop regimen. METHODS: Participants were randomised to tafluprost (Group 1; n = 33) or bimatoprost (Group 2; n = 31). At month 3, each group switched to the opposite treatment. IOP was evaluated at multiple timepoints. MAIN OUTCOME MEASURES: The primary outcome was difference in mean IOP between the two groups at the final visit. Secondary outcomes included change from baseline IOP at month 3 and month 6, difference in mean IOP at month 3 and difference in IOP at all timepoints. Safety outcomes included best-corrected visual acuity (BCVA), adverse events, ocular tolerability, optic nerve assessment and slit lamp biomicroscopy. RESULTS: Both medications significantly lowered IOP at month 6 compared to baseline: 5.4 mmHg (27%) for tafluprost and 6.8 mmHg (33%) for bimatoprost (p < 0.0001). No significant differences in any of the safety measures (including conjunctival hypearemia) were detected. CONCLUSIONS AND RELEVANCE: Bimatoprost produced a statistically significant greater IOP reduction compared to tafluprost with minimal to no difference in side effects. This should be borne in mind when weighing up the pros and cons of preserved versus preservative-free prostaglandin analogue therapy. CLINICALTRIALS.GOV IDENTIFIER: NCT02471105.
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PURPOSE: To investigate the benefit of preoperative treatment with either topical nonsteroidal anti-inflammatory drug (NSAID) or steroid in terms of clinical outcomes following trabeculectomy. DESIGN: Prospective, randomized placebo-controlled trial. PARTICIPANTS: Sixty-one patients. METHODS: Between July 2005 and October 2007, 61 consecutive medically uncontrolled glaucoma patients scheduled for first-time trabeculectomy were randomized to 1 of 3 study topical medication groups: nonsteroidal anti-inflammatory drugs (ketorolac), steroids (fluorometholone), or placebo (artificial tears). Patients instilled 1 drop 4 times daily for 1 month before the procedure and were examined on days 1 and 2, at weeks 1, 2, and 4, and at months 3, 6, 12, 18, and 24 after trabeculectomy. MAIN OUTCOME MEASURES: Incidence of postoperative surgical or medical interventions (needling, laser suture lysis, needling revision, and intraocular pressure [IOP]-lowering medication). RESULTS: Fifty-four patients (54 eyes) were entered for analysis. The mean number of preoperative medications was 2.3+/-0.9. The mean baseline IOP was 21.0+/-6.0 mmHg. The mean postoperative target IOP was 16.5+/-1.8 mmHg. The mean follow-up was 23.6+/-4.0 months. The percentage of patients requiring needling within the first year was 41% in the placebo group, 6% in the NSAID, and 5% in the steroid group (P = 0.006). The percentage of patients requiring IOP-lowering medication to reach the target IOP at 1 year was 24% in the placebo group, 18% in the NSAID group, and 0% in the steroid group (P = 0.054 overall; P = 0.038 for steroids vs. others). The log-rank test showed a significant (P = 0.019) difference in medication-free survival curves between the different groups. More specifically, patients in the steroid group needed significantly less medication over the total follow-up (P = 0.007). CONCLUSIONS: Topical ketorolac or fluorometholone for 1 month before surgery was associated with improved trabeculectomy outcomes in terms of likelihood of postoperative needling. In the steroid group, there was a significantly reduced need for additional postoperative IOP-lowering medication compared with the other groups. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
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Anti-Inflamatórios não Esteroides/administração & dosagem , Glaucoma/cirurgia , Glucocorticoides/administração & dosagem , Trabeculectomia , Administração Tópica , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/administração & dosagem , Túnica Conjuntiva/efeitos dos fármacos , Túnica Conjuntiva/patologia , Método Duplo-Cego , Feminino , Fibrose/prevenção & controle , Fluormetolona/administração & dosagem , Glaucoma/tratamento farmacológico , Humanos , Pressão Intraocular , Cetorolaco/administração & dosagem , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Complicações Pós-Operatórias/prevenção & controle , Cuidados Pré-Operatórios , Estudos Prospectivos , Resultado do TratamentoRESUMO
PURPOSE: This study aimed to describe the clinical findings and management of eyes affected by uveal effusion syndrome. METHODS: We retrospectively evaluated the charts of 13 eyes of 8 consecutive patients diagnosed with uveal effusion syndrome attending the Ophthalmology Unit of the University Hospitals Leuven, Belgium, between 2007 and 2018. The presenting features, investigations, management, and outcomes were analyzed for each case. RESULTS: Cataract surgery was the predisposing factor for uveal effusion in 6 eyes, 2 bilateral uveal effusions (4 eyes) were considered to be medication-induced, and in 3 eyes, the uveal effusion was described as idiopathic. Fundus examination of 5 of 13 eyes showed bullous choroidal detachment, treated with pars plana vitrectomy with superotemporal sclerectomy or transscleral punction. Fundoscopy showed uveal effusion without serous retinal detachment in 3 eyes. Serous retinal detachment accompanied by uveal swelling was observed in 3 eyes and the 2 remaining eyes presented with uveal swelling only. The 8 nonbullous choroidal detachments were treated in a conservative way. A rapid resolution of subretinal fluid and uveal effusion was observed in all cases. CONCLUSIONS: A conservative approach with acetazolamide treatment or just observation was used in our case series in choroidal detachment without substantial visual loss if, over time, slow improvement was documented. However, further studies are needed to verify the effectiveness of the reported therapy.
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Efusões Coroides/cirurgia , Pressão Intraocular/fisiologia , Esclera/cirurgia , Esclerostomia/métodos , Síndrome da Efusão da Úvea/diagnóstico , Vitrectomia/métodos , Adulto , Efusões Coroides/complicações , Efusões Coroides/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oftalmoscopia , Estudos Retrospectivos , Ultrassonografia , Síndrome da Efusão da Úvea/fisiopatologia , Síndrome da Efusão da Úvea/terapiaRESUMO
PURPOSE: Ultrasound cycloplasty (UCP) acts through the selective coagulation of the ciliary body using high-intensity focused ultrasound (HIFU) technology. The aim of this study was to investigate whether the application of ultrasound beams targeting the ciliary body using an external probe influences astigmatism. METHODS: Multicentre, prospective, single-arm, open-label study in adult patients with primary open-angle glaucoma and moderately uncontrolled intraocular pressure (IOP) under glaucoma medication. The primary outcome was induced corneal astigmatism, calculated from topography, and assessed statistically through vector analysis. Secondary outcomes included induced total astigmatism and mean changes from baseline in best-corrected visual acuity (logMAR) and IOP. Subgroup analysis was performed to assess the impact of device centring on corneal and total induced astigmatism. RESULTS: Fifty eyes were enrolled. Mean age was 69.6 ± 11.3 years. At 1, 3 and 6 months postprocedure, HIFU-induced corneal astigmatism was 0.88 D × 93°, 0.87 D × 106° and 1.16 D × 97°, respectively, while induced total astigmatism was 0.62 D × 103°, 0.42 × 106° and 0.39 × 107°. By the last follow-up, the percentage of patients with <0.50, <1.00, <1.50 and <2.00 D of induced corneal versus total astigmatism was 8.3% versus 46%, 29% versus 66%, 62.5% versus 88% and 79% versus 94%. Visual acuity was statistically significantly impaired at 1 month, but no difference remained by 3 and 6 months postprocedure. CONCLUSION: Ultrasound cycloplasty procedure is associated with increased corneal astigmatism. However, its impact on total refractive astigmatism is less pronounced.